Form Of Congenital Night Blindness Research Articles

Isolation of ON Bipolar Cell Genes via hrGFP-coupled Cell Enrichment Using the mGluR6 Promoter

mGluR6 expression is a characteristic property of retinal ON bipolar cells. mGluR6 is also the causal gene for a form of congenital night blindness. To elucidate physiological and pathological functions of ON bipolar cells and mGluR6, we thought it important to identify genes specifically expressed in them. We thus made transgenic mouse lines expressing humanized Renilla reniformis green fluorescent protein (hrGFP), under the control of the mGluR6 promoter. From their retina, we isolated hrGFP-positive cells by cell sorting, and analysed the gene-expression profile of these cells by using DNA microarray. Further analysis revealed that about half of the initially selected ON bipolar cell genes were expressed in the expected retinal layer. We confirmed previously ambiguous retinal localization of regulator of G-protein signalling 11 (RGS11) and transient receptor potential cation channel, subfamily M, member 1 (TRPM1). In addition, we showed the expression of calcium channel, voltage-dependent, alpha2/delta subunit 3 (Cacna2d3) in ON bipolar cells for the first time. Although we could not completely exclude the possibility that a small population of hrGFP-positive cells might not be ON bipolar cells, these mice as well as our strategy would be highly valuable for the further analysis of ON bipolar cells.

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6

We report three unrelated patients with mutations in the GRM6 gene that normally encodes the glutamate receptor mGluR6. This neurotransmitter receptor has been shown previously to be present only in the synapses of the ON bipolar cell dendrites, and it mediates synaptic transmission from rod and cone photoreceptors to this type of second-order neuron. Despite the synaptic defect, best visual acuities were normal or only moderately reduced (20/15 to 20/40). The patients were night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system (i.e., 2-3 log units above normal). Electroretinograms (ERGs) in response to single brief flashes of light had clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicated a markedly reduced ON response and a nearly normal OFF response. There was no subjective delay in the perception of suddenly appearing white vs. black objects on a gray background. These patients exemplify a previously unrecognized, autosomal recessive form of congenital night blindness associated with a negative ERG waveform.

Acquired unilateral loss of dark adaptation.

Poor dark adaptation is a not uncommon symptom and may occur in a wide variety of diseases but its occurrence in one eye only is far less frequent. When it occurs unilaterally, an obvious ocular disease is generally present to account for it and visual functions other than that of dark adaptation are also depressed. Some subjects with poor dark adaptation may have no demonstrable ocular lesion nor any other defect of visual function. Almost always they have one of the forms of congenital night blindness but sometimes the trouble is the first evidence of a progressive tapeto-retinal degeneration. Electrophysiological studies of the retinal function of these patients have proved to be useful, and Armington and Schwab (I954) have shown that by using electroretinography patients with a non-progressive night blindness can be differentiated from those with a progressive tapeto-retinal degeneration. Auerbach, Godel, and Rowe (i969) have similarly studied a large series of patients with night blindness. They have shown that patients with an apparently stationary night blindness fall into two main groups, but they also note that progression of the condition may occur. An acquired form of night blindness without obvious ocular defects and without disturbance of any other ocular function was described by Kelsey and Arden (I969) in which electrophysiological tests of retinal function suggested a lesion at the level of the bipolar cell layer. Two patients with similar acquired changes which were strictly uniocular are described below.